Review
Growth hormone and insulin-like growth factor-1 (IGF-1) and their influence on cognitive aging

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Abstract

The concept that growth hormone and IGF-1 are required for normal development of the mammalian body and, more recently the brain, is supported by a vast experimental literature. IGF-1 crosses the blood–brain barrier and in recent years, much attention has focused on age-related decreases in serum growth hormone and IGF-1 as potential mechanisms that may influence cognitive function in the elderly. However, interventional studies are needed to establish a definite link between these hormones and function of the aging brain. In rodents, long-term growth hormone/IGF-1 replacement improves learning and memory in aged rats. While the exact mechanism underlying these cognitive improvements is unknown, growth hormone and IGF-1 replacement to aged animals increases neurogenesis, vascular density, and glucose utilization, and alters NMDA receptor subunit composition in brain areas that are implicated in learning and memory. While these observations offer valuable insight into the influence of growth hormone and IGF-1 on neuronal events in the aged mammal, additional functional studies are required to link these changes to cognitive improvements.

Introduction

Growth hormone and its anabolic mediator, insulin-like growth factor-1 (IGF-1), have long been recognized for their critical roles in mammalian growth and development. However, these hormones affect numerous organ systems and participate in diverse processes such as wound healing and glucose homeostasis. Numerous studies have focused on the potential roles of growth hormone and IGF-1 in brain development, neurogenesis, and neuroprotection. Only recently, however, have scientists explored the possible benefits of growth hormone and IGF-1 to the aging brain. This chapter is focused on the potential mechanisms by which upregulation of the growth hormone/IGF-1 axis improves learning and memory in aged rodents and humans.

Section snippets

The growth hormone/IGF-1 axis

Pure bovine growth hormone was first isolated from the pituitary gland by Li et al. (1945) and was subsequently shown to stimulate fatty acid metabolism and amino acid uptake, as well as DNA, RNA and protein synthesis (Corpas et al., 1993, Finkelstein et al., 1972). These actions contribute to its regulatory role in cell division and tissue growth, and, with the exception of fatty acid metabolism, occur via the anabolic mediator insulin-like growth factor-1 (IGF-1). In humans, growth hormone is

Endocrine, paracrine, and autocrine sources

Although the brain, with the exception of the hypothalamus, has not typically been considered a target for growth hormone action, autoradiography has demonstrated the expression of growth hormone receptors in the choroid plexus, hippocampus, pituitary, and spinal cord in rodents, with reduced receptor density observed in the cortex (Zhai et al., 1994). Growth hormone receptors have also been observed in human choroid plexus and growth hormone receptor mRNA has been observed in human brain stem (

Age-related changes to the growth hormone/IGF-1 axis

More than 20 years ago, it was revealed that elderly individuals experience a decline in the ability to secrete growth hormone in response to several stimuli, including insulin-induced hypoglycemia and arginine administration (Laron et al., 1970). Subsequent studies revealed a loss of the nocturnal surges of growth hormone (Carlson et al., 1972, Finkelstein et al., 1972) and a decrease in plasma IGF-1 that paralleled the decline in growth hormone pulses (Johanson and Blizzard, 1981, Rudman et

Summary

The studies summarized here represent a vast literature that supports the requirement of growth hormone and IGF-1 for normal development of the mammalian body and brain. These hormones promote long bone and tissue growth, cardiovascular maturation and function, and work with other hormonal systems to regulate blood glucose levels and reproduction. Furthermore, IGF-1 crosses the blood–brain barrier and promotes neurogenesis and synaptogenesis throughout development and during adulthood. The

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